STRUCTURAL BIOLOGY
Biological structures of the year Nearsighted pictures portend farsighted applications We might be tempted to think that structural biologists were just showing off by unveiling stunning snapshots of cellular machinery if we weren’t so wowed by the implications of their achievements. If there’s a limit to the biological complexity these scientists can tackle with cryo-electron microscopy, X-ray crystallography, and other techniques, it hasn’t been reached yet. Here are three of C&EN’s favorite structures of 2016.—SARAH EVERTS
Megaportal
CREDIT: COURTESY OF CLAUDIA HÖBARTNER (DNAZYME); SCIENCE (NUCLEAR PORE COMPLEX); NAT. CHEM. BIOL. (H DAC6 )
The nuclear pore complex is enormous, both in size and biological importance. The 1,000-Å-wide complex is the gatekeeper for the cell’s nucleus, responsible for moving thousands of proteins, RNA molecules, and nutrients in and out of the organelle. Two independent teams, one led by Martin Beck of the European Molecular Biology Laboratory and the other led by André Hoelz of California Institute of Technology, visualized the overall architecture of the membrane-embedded mega-machinery, which includes 30 types of nucleoporin proteins with a combined mass topping 100 million daltons (Science 2016, DOI: 10.1126/science.aaf0643; DOI: 10.1126/science.aaf1015).
Catalytic machine Surprisingly, a DNA enzyme, or DNAzyme, had never been visualized before this year because researchers had been unable to crystallize this type of catalyst. The feat comes thanks to a team led by Claudia Höbartner and Vladimir Pena of the Max Planck Institute for Biophysical Chemistry, who reported the structure of a DNAzyme called 9DB1, which specializes in stitching together RNA strands. The new structure could enable more rational design of singlestranded DNAzymes for biomedical use (Nature 2016, DOI: 10.1038/ nature16471).
‘Sizzling hot’ drug target Drug developers have been pining for an atomic-resolution image of histone deacetylase 6 (HDAC6), whose matterof-fact name belies the enzyme’s sexier role as a “sizzling hot target” for cancer chemotherapy, explains the University of Pennsylvania’s David W. Christianson. That’s because interfering with HDAC6’s ability to deacetylate important cell scaffold proteins can disrupt cell division and eventually lead to cell death. Two independent teams, one led by Christianson and the other led by Patrick Matthias of the Friedrich Miescher Institute for Biomedical Research, solved the structure of HDAC6 (Nat. Chem. Biol. 2016, DOI: 10.1038/ nchembio.2140; DOI: 10.1038/nchembio.2134). DECEMBER 12/19, 2016 | CEN.ACS.ORG | C&EN
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